1. Field of Invention
The field of the currently claimed embodiments of this invention relates to devices and methods for selective capture and stimulated release of circulating cells.
2. Discussion of Related Art
Circulating tumor cells[1] (CTCs) are cancer cells that shed away from either primary tumor(s) or metastatic sites, and circulate in the peripheral blood as the cellular origin of metastases[2]. The current gold standard for cancer diagnosis requires invasive biopsy and subsequent histopathology analysis of the biopsy samples. However, in early stage metastasis or recurrence, it is difficult to identify the metastatic/recurrence sites for collection tissue biopsies. CTCs can therefore be regarded as a “liquid biopsy” of the tumor that offers convenient access to tumor cells before fatal metastasis occurs. To exploit CTCs as a new cancer “biomarker” that could report disease progression and guide implementation of therapy, significant research endeavors[3] have been devoted to developing diagnostic assays capable of detecting and enumerating CTCs in cancer patients' blood. The major technical challenge is to efficiently and specifically capture the extremely low abundance (a few to hundreds cells/mL) of CTCs among a high number (109 cells/mL) of hematologic cells[4] in blood samples. Based on different working mechanisms, a diversity of CTC assays has been created over the past decades. For example, immunomagnetic separation approaches[5] utilize magnetic beads coated with CTC-specific capture agents (e.g., antibodies or aptamers) to capture CTCs. CellSearch™ Assay based on the immunomagnetic separation is the only FDA-cleared CTC enumeration method that can predict prognostic outcomes in metastatic breast, prostate and colorectal cancer. Recently, there have been several microchip-based technologies[6] developed to address the concerns of low CTC-capture efficiency encountered by CellSearch™ Assay. At this juncture, an increasing number of new CTC assays have demonstrated their profound sensitivity for CTC enumeration in cancer patients. In order to further exploit the diagnostic values of CTCs beyond enumeration, current research enterprises are dedicated for establishing molecular and functional analyses of CTCs. It is conceivable that the CTC-derived molecular signatures and functional readouts will provide valuable insight into tumor biology during the critical window where therapeutic intervention could make a significant difference. To pave the way toward molecular and functional analyses of CTCs, there is a desperate need to develop a new CTC assay that can not only capture CTCs with high efficiency, but also release CTCs with minimum contamination of the surrounding white blood cells (WBCs) and negligible disruption to CTCs' viability and functions.